Vitamin B12 and Folate Administration on Homocysteine Concentrations After Nitrous Oxide Anesthesia (Mini-VINO)

The Washington University

Status: Completed

Conditions: Cardiovascular Abnormalities

Treatments: Other: Placebo; Drug: Nitrous oxide (NO) and placebo; Other: oxygen nitrogen; Drug: B12-Folic Acid, nitrous oxide

Study type: Interventional

Funder types: Other

Identifiers

NCT00901394

09-0074

Details and patient eligibility

About

The goal of this study is to find out if giving intravenous B-vitamins before general anesthesia with nitrous oxide prevents the increase in homocysteine, a metabolite that has been linked to cardiovascular complications.

Full description

Patients will be randomized into the following arms:

• Arm A: patients will receive N2O (60% N2O/40% O2) in an open-label fashion during surgery and vitamin supplementation (vitamin B12, 1 mg, and folate, 5 mg) before surgery.
• Arm B: patients will receive N2O 60% N2O/40% O2) in an open-label fashion during surgery and placebo before and after surgery.
• Arm C: patients will not receive N2O, vitamin supplementation, or placebo during/before surgery. Patients in this arm will not be randomized.

Patients will have blood drawn (total of 1-2 teaspoons over 3 days). We will take these samples before their surgery, when their surgery is completed, and in the morning of post-operative day 1. We will be checking their troponin I and troponin T, homocysteine, Vitamin B12, and folate levels. We will also perform a 12-lead EKG. Before and after surgery for patients in Arm A or B, will receive either vitamin B12 (1 mg) and folic acid (5 mg) (or placebo) added to their IV infusion. We also plan to use a non-invasive test known as a nerve conduction study to measure the function of their nerve system. Briefly, 2 small electrodes are attached to their skin over a nerve and, like an EKG, faint electrical pulses are generated and recorded. A typical nerve conduction measurement lasts about 10 minutes.

After the patients surgery we will do genetic testing of MTHFR genotype.

All study samples have been collected.

Of note: there were no secondary outcomes.

Enrollment: 63 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients scheduled for elective surgery with expected duration > 2 hours
• Healthy patients undergoing moderate surgery where the use of N2O is unproblematic

Exclusion criteria

• Contraindication against N2O (pneumothorax, mechanical bowel obstruction, middle ear occlusion, laparoscopic surgery, raised intracranial pressure)
• Patients requiring supplemental oxygen
• Urgent or emergent surgery
• Patients with vitamin B12 or folate deficiency or megaloblastic anemia
• Patients with seizure disorder (epilepsy)
• Allergy or hypersensitivity against IV cobalamin or folate
• Patients with Leber's disease (hereditary optic nerve atrophy)
• Patients taking supplemental vitamin B12 or folate

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

63 participants in 3 patient groups, including a placebo group

Treatment 1

Experimental group

Description:

B12-Folic acid, nitrous oxide

Treatment:

Drug: B12-Folic Acid, nitrous oxide

Drug: Nitrous oxide (NO) and placebo

Treatment 2

Active Comparator group

Description:

Nitrous oxide (NO) and placebo

Treatment:

Drug: Nitrous oxide (NO) and placebo

Other: Placebo

Control group

Placebo Comparator group

Description:

oxygen nitrogen

Treatment:

Other: oxygen nitrogen

Other: Placebo